Role of beta2-containing nicotinic acetylcholine receptors in auditory event-related potentials.
BACKGROUND
Nicotine improves sensory processing in schizophrenic individuals, as measured by changes in auditory event-related potentials (ERPs). Nicotine administration also alters ERPs in mice by increasing the amplitude and gating of the P20 ERP component while decreasing the amplitude of the N40 ERP component. Less is known about the role of specific nicotinic acetylcholine receptor (nAChR) subtypes.


OBJECTIVE
In this study, we examined whether nAChRs containing the beta2 subunit contribute to nicotine's effects on auditory ERPs.


METHODS
We tested the effect of nicotine in wild-type mice and mice lacking the beta2 nAChR subunit. Mice underwent stereotaxic implantation of stainless steel electrodes located in the CA3 region of the hippocampus, and 50 paired click stimuli were delivered during each drug condition.


RESULTS
There was no significant difference in P20 or N40 amplitude or gating between genotypes during the control condition, suggesting that beta2-containing receptors are not essential for the baseline auditory ERP response. Nicotine increased P20 amplitude and enhanced gating in wild-type and beta2 knockout mice, but only decreased N40 amplitude in wild-type mice. There was no effect of nicotine on N40 gating in either genotype.


CONCLUSIONS
beta2-containing receptors are necessary for nicotine's effects on the N40 component of the mouse auditory ERP. These results suggest that beta2-containing nAChRs modulate sensory processing and may serve as a therapeutic target in schizophrenic individuals.
Rudnick
Noam D
ND
Stanley Center for Experimental Therapeutics, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19312, USA.
Koehler
Christine
C
Picciotto
Marina R
MR
Siegel
Steven J
SJ
D000818:Animals; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D013238:Stereotaxic Techniques
D009538:Nicotine; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic